Over the last two decades, the use of advanced medical imaging, particularly with computed tomography (CT), has increased dramatically with over 80 million CT scans performed annually in the United States (U.S.). Integrating CT into routine care has contributed to the earlier and more accurate diagnosis of disease and injury. However, it has also markedly increased patient exposure to ionizing radiation, a well-established carcinogen. Many past studies of cancer risk have focused on specific human populations, such as Japanese atomic bomb survivors, which differ from the general US population undergoing routine medical imaging, and while most experts agree that radiation from medical imaging is associated with increased risk of cancer, the magnitude of the risk is unknown. We propose to study pregnant women and children enrolled from 1996 to 2017 in four integrated health care delivery systems: Kaiser Permanente (KP) Northern California, KP Southern California, KP Northwest, and Group Health Cooperative. We will use a stratified nested case-control study with counter-matching to comprehensively evaluate patterns of medical imaging, cumulative exposure to radiation, and subsequent risk of pediatric cancers. The cohort will include health plan members <21 y and pregnant women of any age, focusing on in utero or fetal (prenatal), childhood, and adolescent exposures. We estimate approximately 17.5 million patient-years of follow-up in this population-based study, including approximately 754 cases of pediatric leukemia and 2,779 cases of all pediatric cancers combined. The aims are to 1) evaluate patterns of medical imaging and associated radiation exposure in pregnant women and pediatric patients (<21 years); and 2) determine the risk of pediatric cancers (<21 years) associated with a) in utero or fetal exposure to medical imaging, focusing on risk of all pediatric cancers and including children born in the health systems with mothers enrolled during pregnancy; b) pediatric exposure to medical imaging, focusing on leukemia and including children born in the health systems; and c) in utero and pediatric exposures, focusing on all pediatric cancers and including children born in the health systems with mothers enrolled during pregnancy. The use of medical imaging with ionizing radiation remains high in the U.S., thus the potential harmful effects of this imaging must be understood so they can be weighed against its diagnostic benefit. This is especially critical for children, because they are particularly vulnerale to the carcinogenic effects of radiation given their rapid growth; in addition, their longer life expectancy gives them more time after exposure than adults to develop a cancer. This proposed study by an inter-disciplinary group of experienced investigators uses unparalleled data resources on U.S. exposure to medical imaging, complete capture of member health care utilization, and detailed demographic and cancer diagnosis information to examine these critical patient care and public health issues.